Key points What are the optimal glycemic goals associated with a reduced risk of dementia in older people with type 2 diabetes? Findings In this cohort study of 253,211 people aged 50 years or older with type 2 diabetes, those with a majority (>50%) of glycated hemoglobin concentrations of 9% or greater had the highest risk of dementia. Meaning The results of this study support common clinical guideline recommendations for relaxed glycemic goals in older adults. |
Importance
The levels of glycemic control associated with lower risk of dementia in people with type 2 diabetes are unknown. This knowledge is critical to inform the setting of patient-centered glycemic goals.
Aim
To examine associations between cumulative exposure to various ranges of glycated hemoglobin (HbA 1c) concentrations with dementia risk across sex and racial/ethnic groups and the association of current therapeutic glycemic targets with dementia risk.
Design, environment and participants
This cohort study included members of the Kaiser Permanente Northern California integrated health care system with type 2 diabetes who were 50 years of age or older during the study period from January 1, 1996 to September 30, 2015.
Individuals with less than 2 HbA 1c measurements during the study period, prevalent dementia at baseline, or less than 3 years of follow-up were excluded. Data was analyzed from February 2020 to January 2023.
Exhibitions
Updated cumulative exposure to HbA 1c thresholds. At each HbA 1c measurement, participants were classified according to the percentage of their HbA 1c measurements that fell into the following categories: less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, 9% to less than 10%, and 10% or more of total hemoglobin (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01).
Main results and measures
The diagnosis of dementia was identified using International Classification of Diseases, Ninth Revision codes from inpatient and outpatient encounters. Cox proportional hazards regression models estimated the association of time-varying cumulative glycemic exposure with dementia, adjusting for age, race and ethnicity, baseline health conditions, and number of HbA 1c measurements.
Results
A total of 253,211 participants were included. The mean (SD) age of participants was 61.5 (9.4) years and 53.1% were men. The mean (SD) duration of follow-up was 5.9 (4.5) years .
Participants with more than 50% of HbA 1c measurements at 9%, less than 10%, or 10% or more had a higher risk of dementia compared to those who had 50% or less of measurements in those categories. (HbA 1c 9% to <10%: adjusted hazard ratio [aHR], 1.31 [95% CI, 1.15-1.51]; HbA 1c ≥10%: aHR, 1.74 [95% CI %, 1.62-1.86]).
In contrast, participants with more than 50% HbA 1c concentrations less than 6%, 6% to less than 7%, or 7% to less than 8% had a lower risk of dementia (HbA 1c <6%). : aHR, 0.92 [95% CI, 0.88-0.97], HbA1c 6% to <7%: aHR, 0.79 [95% CI, 0.77-0.81]; HbA 1c 7% to <8%: aHR, 0.93 [95% CI, 0.89-0.97]).
Conclusions and relevance
In this study, the risk of dementia was highest among adults with cumulative HbA 1c concentrations of 9% or greater. These results support the relaxed glycemic goals currently recommended for older people with type 2 diabetes.
